West Ham United play host to Anderlecht on Thursday evening knowing that top spot in Group B will be all but assured if they can record three points at the London Stadium.
Meanwhile, Anderlecht travel to England aware that posting a surprise victory against the Hammers would put them in a strong position to progress further in the Europa Conference League.
Match preview
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There was a time not so long ago when uncertainty emerged regarding David Moyes's future at West Ham, a consequence of a poor start to the new Premier League campaign.
However, Sunday's 3-1 victory against Fulham, which came in controversial circumstances, was the Hammers' fifth win from six games in all competitions.
Another top-seven finish in the Premier League remains the priority for a club currently four points off that position, but Moyes is also keen for West Ham to live up to their tag of favourites in this competition.
Even at the halfway point, the East Londoners are already on the brink of progress, a result of winning each of their opening three fixtures.
A late goal from Gianluca Scamacca made the difference in Belgium last week, and West Ham will move into an unassailable eight-point lead over their opponents if they can complete the double in England's capital.
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From Anderlecht's perspective, it was a case or so close yet so far last week as they gave a strong account of themselves against superior opposition.
West Ham goalkeeper Alphonse Areola pulled off a stunning save to deny Fabio Silva during the closing stages, preventing the home side from earning what would have felt like a deserved share of the spoils.
Nevertheless, Anderlecht remain on course to reach the last 32 of this competition, holding a one-point lead over Silkeborg in what feels like a race for second place.
With Thursday's encounter representing their toughest in the group, head coach Felice Mazzu will be realistic with his expectations ahead of this contest.
That said, a second-half comeback against Mechelen at the weekend has generated some momentum ahead of this game, Silva scoring his eight goal of the season to seal a 3-1 success.
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Team News
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Having made nine changes for the Premier League fixture with Fulham, Moyes could name a similar team to the one which started against Anderlecht last week.
That would see Angelo Ogbonna continue his game time in Europe and Flynn Downes handed an other opportunity in midfield, although Michail Antonio will likely sit out the game due to illness.
Jarrod Bowen may be handed a rest, potentially leading to Pablo Fornals deputising in the final third, but Maxwel Cornet is expected to remain absent with a calf injury.
Mazzu could also name a similar side to last week's reverse fixture having opted to make three alterations at the weekend.
However, teenager Mario Stroeykens has put himself in contention for a chance after scoring a double as a half-time substitute against Mechelens.
Kristian Arnstad may miss out in the final third should Mazzu hand a chance to another of his prospects.
West Ham United possible starting lineup:
Areola; Coufal, Dawson, Ogbonna, Johnson, Palmieri; Downes, Lanzini; Benrahma, Scamacca, Fornals
Anderlecht possible starting lineup:
Van Crombrugge; Hoedt, Debast, Delcroix; Murillo, Ashimeru, Diawara, Amuzu; Stroeykens, Verschaeren; Silva
We say: West Ham United 2-0 Anderlecht
Having pushed West Ham all of the way in front of their own supporters, there will be confidence within the Anderlecht ranks that they can earn a result at the London Stadium. However, even with squad rotation, the Hammers should have more than enough quality to post another momentum-building win.
